Evidence for the Existence in Spermatozoa of a Factor Inhibiting the Follicle Stimulating Hormone Releasing Hormone Synthesis

Lugaro, G; Casellato, Maria Maddalena; Mazzola, Giovanni; Fachini, G; Carrea, Giacomo

doi:10.1159/000122293

Cited by 46 publications

(15 citation statements)

References 4 publications

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“…Following the discovery of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the two pituitary hormones known to regulate the development and activity of the gonads, Klinefelter et al (3) postulated that a testicular factor, inhibin, exerted a specific negative feedback action on pituitary FSH secretion. This hypothesis was substantiated when numerous investigators demonstrated a direct suppression of peripheral FSH in animals treated with steroid-free testicular or ovarian preparations (4)(5)(6). Inhibin activity has since been observed in testicular or ovarian extracts and in cultured Sertoli or granulosa cells from a variety of species (7)(8)(9)(10).…”

mentioning

confidence: 96%

Inhibin A-subunit cDNAs from porcine ovary and human placenta.

Mayo¹,

Cerelli²,

Spiess³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

203

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Inhibin, a gonadal protein that preferentially suppresses the secretion of pituitary follicle-stimulating hormone, has been isolated from porcine follicular fluid and characterized as a 32-kDa protein composed of 18-kDa and 14-kDa subunits. In the present work, oligonucleotide probes predicted from amino-terminal inhibin amino acid sequences have been used to isolate, from a porcine ovarian Xgtll cDNA library, clones encoding the 18-kDa subunit, or A chain, of inhibin. DNA sequence analysis showed that the inhibin A chain is initially synthesized as a larger precursor protein and is predicted to be a glycopeptide. Inhibin A-chain mRNA is present specifically in the gonads, and its synthesis can be induced by treatment of the animal with gonadotropins. The porcine probe was used to isolate a human inhibin A-subunit cDNA from a placental cDNA library. The human precursor is highly homologous to its porcine counterpart and is predicted to generate an 18-kDa glycosylated inhibin A subunit.The biological basis for gonadal regulation of pituitary function was formulated in 1923 by Mottram and Cramer (1), who observed hypertrophy of rat pituitary cells following radiation-induced testicular damage. In 1932 McCullaugh (2) demonstrated that the appearance of these hypertrophied cells could be inhibited by the injection of a water-soluble substance derived from bovine testes, and he termed this substance inhibin. Following the discovery of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the two pituitary hormones known to regulate the development and activity of the gonads, Klinefelter et al. (3) postulated that a testicular factor, inhibin, exerted a specific negative feedback action on pituitary FSH secretion. This hypothesis was substantiated when numerous investigators demonstrated a direct suppression of peripheral FSH in animals treated with steroid-free testicular or ovarian preparations (4-6).

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mentioning

confidence: 96%

Inhibin A-subunit cDNAs from porcine ovary and human placenta.

Mayo¹,

Cerelli²,

Spiess³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

203

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“…Additionally, it has been suggested that they may also act on the hypothalamus to indirectly regulate FSH secretion [12][13][14]. The presence of activin/inhibin pA and Pb subunit-stained terminals in the reReceived: September 20, 1990 Accepted after revision: March 4, 1991 gions of the septal and the preoptic areas, where neurons con taining GnRH are found, suggests that activin, and possibly in hibin, may act on the hypothalamus to regulate GnRH expres sion an d /o r secretion [15].…”

mentioning

confidence: 99%

Activin-A Modulates Gonadotropin-Releasing Hormone Secretion from a Gonadotropin-Releasing Hormone-Secreting Neuronal Cell Line

et al. 1991

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The recent development of GnRH-secreting neuronal cell lines (GT1-1, GT1-3 and GT1-7 clones) has provided a model system for the study of the neural regulation of GnRH expression and secretion. We report here that activin-A stimulates GnRH secretion by GT1-7 cells in a dose-dependent manner, with an EC50 of ∼2.5 ng/ml. The maximal response (50% stimulation) was achieved after 2 days of incubation with 20 ng/ml activin-A. Activin-A treatment increased total GnRH (secreted + cellular) in GT1-7 cells, possibly reflecting a stimulation of GnRH biosynthetic rates. The secretory effect of activin-A was also accompanied by a change in the cellular morphology to a more neuronal phenotype. The addition of TGF-β (10 ng/ml), which is structurally related to activins, did not significantly increase secretion of GnRH by GT1-7 cells illustrating the specificity of the activin effect on this cell line. Although inhibin (20 ng/ml) alone did not directly affect the spontaneous secretion of GnRH, it was able to partially block the stimulatory effect of activin. The present study with the GT1-7 clonal cell line suggests that activin, and perhaps inhibin, might act at hypothalamic sites to regulate reproduction through the control of GnRH production and/or secretion.

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“…It seems possible that inhibin acts at the pituitary as well as the hypothalamus level [74]. If inhibin acts on the pituitary, it should modulate the stimulation exerted by GnRH.…”

Section: Mode Of Action Of Inhibinmentioning

confidence: 99%

“…Lugaro et al [74] administered apeptidic factor isolated from bull spermatozoa into the lateral ventricle of castrated male rats, which suppressed serum FSH levels and GnRH activity, but not LH.…”

Section: Mode Of Action Of Inhibinmentioning

confidence: 99%

Male and Female Inhibin

Hafez

1980

Archives of Andrology

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The testis and ovary secrete a nonsteroidal hormone that selectively inhibits pituitary FSH secretion. Inhibin, a polypeptide hormone produced by Sertoli cells in the seminiferous tubules and by the granulosa cells of the ovarian follicle, is isolated from seminal fluid, rete testis fluid testicular and ovarian extracts, and follicular fluid. There may be two forms of inhibin. a form of higher molecular weight (> 10,000 daltons) being the precursor of a low-moleculay-weight form (>5,000 daltons). The functional integrity of inhibin is destroyed by trypsin or pepsin digestion and exposure to heat. This induces the formation of antibodies that are able to neutralize endogenous inhibin when injected into adult males or females. Apart from its main action at the pituitary level, inhibin could also function at the hypothalamus or directly at the gonad. Inhibin inhibits the release of FSH and to a lesser extent of LH induced by exogenous GnRH in vivo and in vitro. Inhibin reduces the endogenous GnRH content of hypothalami maintained in organ culture. These reactions have been utilized in the development of in vivo and in vitro assay methods. It is feasible that inhibin is involved in the regulation of the ovarian cycle, and that this hormone plays a more important role in the feedback regulation of FSH in the adult female than in the adult male.

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Evidence for the Existence in Spermatozoa of a Factor Inhibiting the Follicle Stimulating Hormone Releasing Hormone Synthesis

Cited by 46 publications

References 4 publications

Inhibin A-subunit cDNAs from porcine ovary and human placenta.

Inhibin A-subunit cDNAs from porcine ovary and human placenta.

Activin-A Modulates Gonadotropin-Releasing Hormone Secretion from a Gonadotropin-Releasing Hormone-Secreting Neuronal Cell Line

Male and Female Inhibin

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